Microbiology, 2021

14 • Summary 605
cells.
• Because it can easily mutate to become drug
resistant, HIV is typically treated with a
combination of several antiretroviral drugs,
which may include reverse transcriptase
inhibitors, protease inhibitors, integrase
inhibitors, and drugs that interfere with viral
binding and fusion to initiate infection.
14.5 Drug Resistance
• Antimicrobial resistance is on the rise and is
the result of selection of drug-resistant strains
in clinical environments, the overuse and
misuse of antibacterials, the use of
subtherapeutic doses of antibacterial drugs, and
poor patient compliance with antibacterial drug
therapies.
• Drug resistance genes are often carried on
plasmids or in transposons that can undergo
vertical transfer easily and between microbes
through horizontal gene transfer.
• Common modes of antimicrobial drug
resistance include drug modification or
inactivation, prevention of cellular uptake or
efflux, target modification, target
overproduction or enzymatic bypass, and target
mimicry.
• Problematic microbial strains showing
extensive antimicrobial resistance are
emerging; many of these strains can reside as
members of the normal microbiota in
individuals but also can cause opportunistic
infection. The transmission of many of these
highly resistant microbial strains often occurs
in clinical settings, but can also be communityacquired.
14.6 Testing the Effectiveness of
Antimicrobials
• The Kirby-Bauer disk diffusion test helps
determine the susceptibility of a microorganism
to various antimicrobial drugs. However, the
zones of inhibition measured must be
correlated to known standards to determine
susceptibility and resistance, and do not provide
information on bactericidal versus
bacteriostatic activity, or allow for direct
comparison of drug potencies.
• Antibiograms are useful for monitoring local
trends in antimicrobial resistance/susceptibility
and for directing appropriate selection of
empiric antibacterial therapy.
• There are several laboratory methods available
for determining the minimum inhibitory
concentration (MIC) of an antimicrobial drug
against a specific microbe. The minimal
bactericidal concentration (MBC) can also be
determined, typically as a follow-up experiment
to MIC determination using the tube dilution
method.
14.7 Current Strategies for
Antimicrobial Discovery
• Current research into the development of
antimicrobial drugs involves the use of highthroughput
screening and combinatorial
chemistry technologies.
• New technologies are being developed to
discover novel antibiotics from soil
microorganisms that cannot be cultured by
standard laboratory methods.
• Additional strategies include searching for
antibiotics from sources other than soil,
identifying new antibacterial targets, using
combinatorial chemistry to develop novel drugs,
developing drugs that inhibit resistance
mechanisms, and developing drugs that target
virulence factors and hold infections in check.